Macrophages have a diverse range of activities in immunologic and inflammatory reactions. These cells have recently been recognized to be a final common pathway for the clearance and degradation of proteases released extracellularly by neutrophils. They possess cell surface receptors which are capable of binding human leukocyte elastase (HLE) directly, as well as other receptors which bind proteases that are complexed with alpha-2-macroglobulin. Macrophage clearance of HLE has been accorded particular importance because this enzyme has been implicated in the pathogenesis of tissue injury in a variety of disease states, including human pulmonary emphysema. The objective of this proposal is to clarify the importance of macrophages in the direct binding, internalization and degradation of products released by neutrophils. Particular emphasis will be placed upon the role of the alveolar macrophage in ameliorating lung injury due to neutrophilic inflammation. The following specific aims will be addressed: (l) Characterization of the direct binding and internalization of HLE by human alveolar macrophages, and examination of its fate following internalization; (2) Clarification of the interrelationships among macrophage binding of HLE, lactoferrin and other neutrophil glycopropteins; (3) Evaluation of the role of alveolar macrophages in protecting lung connective tissue against HLE 'in vivo'. These studies will provide into macrophage-neutrophil interactions in inflammatory processes and will extent understanding of macrophage surface receptors. The results should help elucidate mechanisms for disposal of extracellular proteases and, in particular, aid understanding of lung defenses against proteases.